Document Detail


Molecular dissection of telomeric repeat-containing RNA biogenesis unveils the presence of distinct and multiple regulatory pathways.
MedLine Citation:
PMID:  20713443     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Telomeres are transcribed into telomeric repeat-containing RNA (TERRA), large, heterogeneous, noncoding transcripts which form part of the telomeric heterochromatin. Despite a large number of functions that have been ascribed to TERRA, little is known about its biogenesis. Here, we present the first comprehensive analysis of the molecular structure of TERRA. We identify biochemically distinct TERRA complexes, and we describe TERRA regulation during the cell cycle. Moreover, we demonstrate that TERRA 5' ends contain 7-methylguanosine cap structures and that the poly(A) tail, present on a fraction of TERRA transcripts, contributes to their stability. Poly(A)(-) TERRA, but not poly(A)(+) TERRA, is associated with chromatin, possibly reflecting distinct biological roles of TERRA ribonucleoprotein complexes. In support of this idea, poly(A)(-) and poly(A)(+) TERRA molecules end with distinct sequence registers. We also determine that the bulk of 3'-terminal UUAGGG repeats have an average length of 200 bases, indicating that the length heterogeneity of TERRA likely stems from its subtelomeric regions. Finally, we find that TERRA is regulated during the cell cycle, being lowest in late S phase and peaking in early G(1). Our analyses offer the basis for investigating multiple regulatory pathways that affect TERRA synthesis, processing, turnover, and function.
Authors:
Antonio Porro; Sascha Feuerhahn; Patrick Reichenbach; Joachim Lingner
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-08-16
Journal Detail:
Title:  Molecular and cellular biology     Volume:  30     ISSN:  1098-5549     ISO Abbreviation:  Mol. Cell. Biol.     Publication Date:  2010 Oct 
Date Detail:
Created Date:  2010-09-23     Completed Date:  2010-10-28     Revised Date:  2014-02-19    
Medline Journal Info:
Nlm Unique ID:  8109087     Medline TA:  Mol Cell Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  4808-17     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Base Sequence
Cell Cycle
Cell Line
HeLa Cells
Humans
RNA / biosynthesis*,  genetics*
RNA Caps / metabolism
RNA Processing, Post-Transcriptional
RNA Stability
RNA, Messenger / metabolism
Subcellular Fractions / metabolism
Tandem Repeat Sequences
Telomere / genetics*,  metabolism*
Grant Support
ID/Acronym/Agency:
232812//European Research Council
Chemical
Reg. No./Substance:
0/RNA Caps; 0/RNA, Messenger; 63231-63-0/RNA
Comments/Corrections

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